DESCRIPTION (Applicant's Description): P27 and p21 are two recently discovered proteins which cause a G1 block to cell cycle progression in response to antimitogenic stimuli. Elimination of cell cycle checkpoints mediated by molecules such as these may contribute to cellular transformation or tumor progression. Dr. Fero, an oncologist who completed his medical training at the University of Washington and the Fred Hutchinson Cancer Research Center, has created transgenic mice in order to test these hypotheses. These mice will be studied to assess the overall phenotypic effect of p27 and p21 disruption alone and in combination. The susceptibility of these mice to the development of mammary and skin tumors, both spontaneously and following exposure to carcinogens, will then be determined. The project involves collaboration of scientists from the Basic Sciences and Public Health divisions of the Hutchinson Center with scientists at the Hematology and Biochemistry divisions of the University of Washington. Dr. Fero will enhance his basic science background further by combining molecular genetics and biostatistics coursework to his research program. His goals are to develop transgenic animal models which help to unravel the mysteries of cell cycle regulation and will contribute to the development of new classes of cancer therapeutic agents.